Are the average gait speeds during the 10 meter and 6 minute walk tests redundant in Parkinson disease?

Published in final edited form as: Gait Posture. 2017 February ; 52: 178–182. doi:10.1016/j.gaitpost.2016.11.033.We investigated the relationships between average gait speed collected with the 10Meter Walk Test (Comfortable and Fast) and 6Minute Walk Test (6MWT) in 346 people with Parkinson disease (PD) and how the relationships change with increasing disease severity. Pearson correlation and linear regression analyses determined relationships between 10Meter Walk Test and 6MWT gait speed values for the entire sample and for sub-samples stratified by Hoehn & Yahr (H&Y) stage I (n=53), II (n=141), III (n=135) and IV (n=17). We hypothesized that redundant tests would be highly and significantly correlated (i.e. r>0.70, p<0.05) and would have a linear regression model slope of 1 and intercept of 0. For the entire sample, 6MWT gait speed was significantly (p<0.001) related to the Comfortable 10 Meter Walk Test (r=0.75) and Fast 10Meter Walk Test (r=0.79) gait speed, with 56% and 62% of the variance in 6MWT gait speed explained, respectively. The regression model of 6MWT gait speed predicted by Comfortable 10 Meter Walk gait speed produced slope and intercept values near 1 and 0, respectively, especially for participants in H&Y stages II-IV. In contrast, slope and intercept values were further from 1 and 0, respectively, for the Fast 10Meter Walk Test. Comfortable 10 Meter Walk Test and 6MWT gait speeds appeared to be redundant in people with moderate to severe PD, suggesting the Comfortable 10 Meter Walk Test can be used to estimate 6MWT distance in this population.This study was funded by the Davis Phinney Foundation, the Parkinson's Disease Foundation, and the National Institutes of Health (R01 NS077959, K12 HD055931, UL1 TR000448). The funding sources had no input related to study design, data collection, or decision to submit for publication. (Davis Phinney Foundation; Parkinson's Disease Foundation; R01 NS077959 - National Institutes of Health; K12 HD055931 - National Institutes of Health; UL1 TR000448 - National Institutes of Health

Cyclooxygenase-1 and -2 modulate sweating but not cutaneous vasodilation during exercise in the heat in young men

We recently reported that the nonselective cyclooxygenase (COX) inhibitor ketorolac attenuated sweating but not cutaneous vasodilation during moderate‐intensity exercise in the heat. However, the specific contributions of COX‐1 and COX‐2 to the sweating response remained to be determined. We tested the hypothesis that COX‐1 but not COX‐2 contributes to sweating with no role for either COX isoform in cutaneous vasodilation during moderate‐intensity exercise in the heat. In thirteen young males (22 ± 2 years), sweat rate and cutaneous vascular conductance were measured at three forearm skin sites that were continuously treated with (1) lactated Ringer\u27s solution (Control), (2) 150 μmmol·L−1 celecoxib, a selective COX‐2 inhibitor, or (3) 10 mmol L−1 ketorolac, a nonselective COX inhibitor. Participants first rested in a non heat stress condition (≥85 min, 25°C) followed by a further 70‐min rest period in the heat (35°C). They then performed 50 min of moderate‐intensity cycling (~55% peak oxygen uptake) followed by a 30‐min recovery period. At the end of exercise, sweat rate was lower at the 150 μmol·L−1 celecoxib (1.51 ± 0.25 mg·min−1·cm−2) and 10 mmol·L−1 ketorolac (1.30 ± 0.30 mg·min−1·cm−2) treated skin sites relative to the Control site (1.89 ± 0.27 mg·min−1·cm−2) (both P ≤ 0.05). Additionally, sweat rate at the ketorolac site was attenuated relative to the celecoxib site (P ≤ 0.05). Neither celecoxib nor ketorolac influenced cutaneous vascular conductance throughout the experiment (both P > 0.05). We showed that both COX‐1 and COX‐2 contribute to sweating but not cutaneous vasodilation during moderate‐intensity exercise in the heat in young men

Ramucirumab in combination with pembrolizumab in treatment-naïve advanced gastric or gej adenocarcinoma: Safety and antitumor activity from the phase 1a/b jvdf trial

Ramucirumab (anti-VEGFR2) plus pembrolizumab (anti-PD1) demonstrated promising antitumor activity and tolerability among patients with previously treated advanced cancers, supporting growing evidence that combination therapies modulating the tumor microenvironment may expand the spectrum of patients who respond to checkpoint inhibitors. Here we present the results of this combination in first-line patients with metastatic G/GEJ cancer. Twenty-eight patients (≥18 years) with no prior systemic chemotherapy in the advanced/metastatic setting received ramucirumab (8 mg/kg days 1 and 8) plus pembrolizumab (200 mg day 1) every 3 weeks as part of JVDF phase 1a/b study. The primary endpoint was safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and overall survival (OS). Tumors were PD-L1-positive (combined positive score ≥ 1) in 19 and-negative in 6 patients. Eighteen patients experienced grade 3 treatment-related adverse events, most commonly hypertension (14%) and elevated alanine/aspartate aminotransferase (11% each), with no grade 4 or 5 reported. The ORR was 25% (PD-L1-positive, 32%; PD-L1-negative, 17%) with duration of response not reached. PFS was 5.6 months (PD-L1-positive, 8.6 months; PD-L1-negative, 4.3 months), and OS 14.6 months (PD-L1-positive, 17.3 months; PD-L1-negative, 11.3 months). Acknowledging study design limitations, ramucirumab plus pembrolizumab had encouraging durable clinical activity with no unexpected toxicities in treatment-naïve biomarker-unselected metastatic G/GEJ cancer, and improved outcomes in patients with PD-L1-positive tumors

The Agricultural Matrix and a Future Paradigm for Conservation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73889/1/j.1523-1739.2006.00582.x.pd

Evaluation of the current knowledge limitations in breast cancer research: a gap analysis

BACKGROUND A gap analysis was conducted to determine which areas of breast cancer research, if targeted by researchers and funding bodies, could produce the greatest impact on patients. METHODS Fifty-six Breast Cancer Campaign grant holders and prominent UK breast cancer researchers participated in a gap analysis of current breast cancer research. Before, during and following the meeting, groups in seven key research areas participated in cycles of presentation, literature review and discussion. Summary papers were prepared by each group and collated into this position paper highlighting the research gaps, with recommendations for action. RESULTS Gaps were identified in all seven themes. General barriers to progress were lack of financial and practical resources, and poor collaboration between disciplines. Critical gaps in each theme included: (1) genetics (knowledge of genetic changes, their effects and interactions); (2) initiation of breast cancer (how developmental signalling pathways cause ductal elongation and branching at the cellular level and influence stem cell dynamics, and how their disruption initiates tumour formation); (3) progression of breast cancer (deciphering the intracellular and extracellular regulators of early progression, tumour growth, angiogenesis and metastasis); (4) therapies and targets (understanding who develops advanced disease); (5) disease markers (incorporating intelligent trial design into all studies to ensure new treatments are tested in patient groups stratified using biomarkers); (6) prevention (strategies to prevent oestrogen-receptor negative tumours and the long-term effects of chemoprevention for oestrogen-receptor positive tumours); (7) psychosocial aspects of cancer (the use of appropriate psychosocial interventions, and the personal impact of all stages of the disease among patients from a range of ethnic and demographic backgrounds). CONCLUSION Through recommendations to address these gaps with future research, the long-term benefits to patients will include: better estimation of risk in families with breast cancer and strategies to reduce risk; better prediction of drug response and patient prognosis; improved tailoring of treatments to patient subgroups and development of new therapeutic approaches; earlier initiation of treatment; more effective use of resources for screening populations; and an enhanced experience for people with or at risk of breast cancer and their families. The challenge to funding bodies and researchers in all disciplines is to focus on these gaps and to drive advances in knowledge into improvements in patient care

Oral Disposition Index Predicts the Development of Future Diabetes Above and Beyond Fasting and 2-h Glucose Levels

OBJECTIVE—We sought to determine whether an oral disposition index (DIO) predicts the development of diabetes over a 10-year period. First, we assessed the validity of the DIO by demonstrating that a hyperbolic relationship exists between oral indexes of insulin sensitivity and β-cell function